Is APC p.Val543= (c.1629T>C) pathogenic?

APC p.Val543= (c.1629T>C) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-10-03). Very rare (popmax 0.00447%, eas); Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Val543= (c.1629T>C)?

APC p.Val543= (c.1629T>C) is associated with classic or attenuated familial adenomatous polyposis, hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Val543= (c.1629T>C) in the general population?

APC p.Val543= (c.1629T>C) is very rare (popmax 0.00447%, eas) (gnomAD).

APC p.Val543=

c.1629T>C · rs779848042 · VCV217934

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.23, phastCons 1
Overall
CADD	13.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% East Asian · 2/44,750 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000125% 2/1,603,334 alleles · very rare exomes 2/1,450,996 · genomes 0/152,338 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APC
Protein: p.Val543=
Coding: c.1629T>C
MANE Select: NM_000038
dbSNP: rs779848042
Type: single nucleotide variant
Location: chr5:112828858 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 543: an α-helix

Full APC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

classic or attenuated familial adenomatous polyposis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome familial adenomatous polyposis 1

Similar variants

APC p.Val543Phe Uncertain significance ★★★ ⚠ same residue
APC p.Val543Ala Uncertain significance ★ ⚠ same residue
APC p.Val543Ile Uncertain significance ★ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G Pathogenic ★★★ same condition
APC c.1312+5G>A Likely pathogenic ★★★ same condition
APC c.1312+5G>C Likely pathogenic ★★★ same condition
APC c.1409-3T>G Likely pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/apc-p-val543 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown